A small but antigenically significant amount of intact food proteins is absorbed at the intestinal level. These proteins are transported by an endocytotic mechanism mostly in degraded form via the lysosomal pathway of the enterocytes, but those that escape lysosomal degradation appear to be a small fraction of potential food antigens that enter the body. To establish whether protein uptake and processing are similar between mature and immature enterocytes, villus and crypts cells were isolated from the small intestine of adult mice. In each fraction, we measured lysosomal cathepsin activities and cell binding, uptake, and degradation of horseradish peroxidase (HRP). The following results were observed: (a) mice exhibited an increasing villus-to-crypt gradient of cathepsins B and D; (b) binding, internalization and degradation of HRP were twice as high in crypt cells as in villus cells, indicating that the rate of endocytosis in crypt cells doubled; and (c) the percentage of intracellular intact and degraded HRP remained similar in both cell types, suggesting that lysosomal degradation was not the limiting step of endocytosis. Chloroquine and ammonia increased intracellular intact HRP, but monensin did not. These results suggest that intestinal villus and crypt cells do not transfer proteins at the same rate. This may have important biological consequences in physiopathological states in which the crypt/villus ratio is greatly increased.